Rhesus Cytomegalovirus vaccine vectors expressing Simian Immunodeficiency Virus proteins (RhCMV/SIV) provide protection from pathogenic SIV (Hansen S G et al., Nat Med 15, 293 (2009); Hansen S G et al., Nat 473, 523 (2011); both of which are incorporated by reference herein). This protection is fundamentally distinct from other T cell vaccines in its extreme efficacy and nearly instantaneous onset, with ˜50% of vaccines manifesting complete control of viral replication following a profoundly blunted and contracted acute phase of viremia. Although RhCMV-protected macaques exhibited periodic low-level “blips” of viremia, CD4+ memory T cell depletion was not observed, SIV-specific antibody responses did not develop, and subsequently, over time, viral nucleic acid became barely quantifiable while replication competent virus disappeared from the tissues of protected animals. These events did not occur in spontaneous SIV elite controllers and DNA prime/Ad5 boost vaccinated controllers (Hansen S G et al., Nature 502, 100 (2013); incorporated by reference herein). Given the central role of RhCMV-induced CD8+ T cells in mediating this protective effect in RhCMV/SIV-vaccinated macaques, defining the functional properties of these T cells is critical to understanding their mechanistic contribution to RhCMV/SIV vector-induced control of SIV replication. Understanding these properties may in turn lead to new uses for cytomegalovirus vaccine vectors expressing heterologous antigens.
CMVs may establish latency and reactivate in cells of the myeloid lineage, and macrophages play a central role in viral dissemination. In addition, dendritic cells are essential antigen presenting cell in vivo. CMV vectors that express heterologous antigens specifically constructed that they fail to replicate in such cells may be used as new vaccine candidates eliciting a modified, unconventional immune profile.